Medical apparatus, for example, medical devices such as contact lenses, catheters for vascular access (both arterial and venous), abdominal cavity tubing, drainage bags and connectors of various kinds, are required to be infection resistant. The desirable feature of such medical apparatus is control of infection that occurs during the application of the 20, apparatus when in contact with body tissue or fluid. The term medical device as used herein is intended to encompass the full range of devices for intimate contact with the human or other mammalian body, or with the corresponding body fluids, as implants, prostheses, interface devices, surgical equipment and the like.
Fabrication of medical apparatus is usually from polymeric materials that may comprise, but are not limited to, polyurethanes, silicones, polyvinylchloride and others, by moulding and extrusion techniques.
There are many cited efforts to eradicate the problem of infection on medical apparatus. These have largely been aimed at attaching the infection resistant material to the polymeric apparatus.
U.S. Pat. No. 3,695,921 discloses a layer of hydrophilic polymer on a catheter that is able to absorb an antibiotic. Thermoplastic polyurethane medical devices containing an anti-microbial agent on their surface are described.
U.S. Pat. No. 4,581,028 discloses infection resistant vascular grafts with incorporated anti-microbial agents, such as silver sulphadiazine and pipericillin.
U.S. Pat. No. 4,479,795 describes medical apparatus of permeable polymers, which incorporate releasable anti-microbial agent that is able to diffuse to the surface to form a barrier.
As disclosed in a Japanese Patent Application No. 60/36064 chlorhexidine is adsorbed on to the surface of polyurethane or silicone catheter by dipping into an aqueous solution of chlorhexidine and then converted to a water insoluble form by dipping into a solution of an acid.
Japanese Patent Application No 59/228,856 discloses an elastomeric catheter possessing a water insoluble biguanide or salt as a thin coating on the surface.
PCT Application No WO 86/02561 discloses a thermoplastic polymer having up to 1% chlorhexidine contained in or upon the surface.
UK Patent Application No 2,084,466A discloses a procedure for rendering polypropylene apparatus biocidal with chlorhexidine base, and suggests that the apparatus may be prepared from other plastics.
Solomon at el., in U.S. Pat. No. 4,713,402, discloses the bonding of a quaternary salt to the surface of a polymeric apparatus and the attachment of an antibiotic to the salt.
In U.S. Pat. No. 4,678,660 there is disclosure of a polyurethane article having on the surface a layer of a polyurethane alloy consisting of a dispersed complex of a quaternary salt with an antibiotic.
Solomon et al. describe in U.S. Pat. No. 5,451,424 a method for preparing medical apparatus by a homogenous melt of polymer and chlorhexidine and having bulk distributed chlorhexidine
U.S. Pat. No. 4,891,423 discloses linear polyoxyalkylene diamine biguanides and discusses other known biguanides, and their use in solid and liquid bactericidal and fungicidal compositions, including ophthalmic saline solutions.
U.S. Pat. No. 5,142,010 discloses the vinyl copolymerisation of certain polymerisable unsymmetrical biguanide compounds.
U.S. Pat. No. 5,817,325 discloses crosslinking biguanide polymers with, inter alia, isocyanates or epoxides to form an immobile, insoluble, non-leachable surface matrix which has the ability to deliver deposited biocidal silver salts into a the interior of a micro-organism. The polymers are useful for coating contact lens cases and other articles. The biocidal action is through the silver salts, not through the highly cross-linked biguanides.
Even though the methods for preparing infection resistant medical apparatus have addressed some of the problems, they are, however, not adequately effective. A major constraint is that the infection resistant material, when incorporated on to or into the apparatus, loses potency in inhibiting or reducing bacterial growth.
Another contributing factor is that the bulk distribution of the infection resistant material is not stable and in certain cases is able to permeate from the apparatus into body tissue or fluid and cause harmful effects.